Reconstitution of cytomegalovirus specific T cells after pediatric allogeneic stem cell transplantation: results from a pilot study using a multi-allele CMV tetramer group.
BACKGROUND
Recovery of cytomegalovirus (CMV)-specific T cell mediated immunity after allogeneic hematopoietic stem cell transplantation (SCT) is critical for protection against CMV disease. Tetramer-based technologies have been shown to be a sensitive tool in the enumeration of specific T cells, but have the disadvantage of HLA-restriction of the peptides.


METHODS
In this pilot study, we tested the feasibility of a panel of 6 CMV-specific tetrameric HLA/CMV-peptide complexes to enumerate CMV-specific CD8 +T cells (CTLs). The reconstitution of CMV-specific CTLs was assessed in 16 children in the first year after allogeneic SCT (median age, 8 years).


RESULTS
The presented assay covered more than 85% of our patients transplanted in the last 3 years. During CMV-reactivation, all 4 of the 16 analyzed patients with a high virus-load showed less than 10 CMV-specific CTLs/microl; out of these, three had not any detectable CMV-CTLs. On the other hand, five of the children with less than 10 CMV-specific CTLs/microl did not develop CMV reactivation. When enumeration of T cells was performed by means of different tetrameric HLA/CMV-peptide complexes simultaneously, the numbers of CMV-specific CTLs cells widely differed according to the HLA-type.


CONCLUSIONS
Our pilot study suggests that enumeration of CMV-specific T cells by means of a panel of 6 tetramers might be a useful tool in the risk assessment for CMV reactivation in the majority of patients undergoing allogeneic SCT, but future trials have to evaluate whether this method is appropriate in tailoring antiviral therapy in the individual patient.
Koehl
U
U
Pediatric Hematology and Oncology, University Children's Hospital, Frankfurt/Main, Germany. Ulrike.Koehl@kgu.de
Dirkwinkel
E
E
Koenig
M
M
Erben
S
S
Soerensen
J
J
Bader
P
P
Doerr
H W
HW
Preiser
W
W
Weissinger
E
E
Klingebiel
T
T
Martin
H
H
Lehrnbecher
T
T
D000293:Adolescent; D000483:Alleles; D000918:Antibody Specificity / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000175:diagnosis / Q000276:immunology*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D009894:Opportunistic Infections / Q000175:diagnosis / Q000276:immunology*; D010865:Pilot Projects; D014775:Virus Activation / Q000276:immunology
D000956:Antigens, Viral; D007166:Immunosuppressive Agents